1. Field of the Invention
The present invention relates to a capsule for encapsulating implantable cells for improving the detectability of electrical signals generated by the cells. The invention also relates to a method of making the capsule, and a constituent detection system in which the capsule is used.
2. Description of the Related Art
The immune system is responsible for the phenomenon of rejection, i.e. destruction of cells or tissues taken from one person or species and implanted in another. The rejection is stronger when the implant's origin is from another species. To reduce this problem in human-to-human or animal-to-animal implants, tissue type matching procedures are employed and intensive immuno-suppressive drug treatment is given to the recipient, usually for life.
An alternative technique that enables autografting (in the same species), as well as xenografting (between different species) is to enclose the implant in a sealed capsule made out of semi-permeable membrane. The membrane is permeable to small molecules and impermeable to large molecules. The cut-off permeability level is usually at molecular weights of about 30,000-50,000. This cut-off level allows nutrients, gases, excretions etc. to pass through the membrane into and out of the implanted cells, and at the same time prevents cells and large molecules, such as proteins and antibodies, from passing through the membrane. This method effectively neutralizes the damaging effects of the immune system. The semi-permeable membranes discriminate between substances by means of sub-microscopic pores, usually 5-50.ANG. in diameter. Examples of such biocompatible membrane materials include PSF (polysulfone) and PVC/PAN (polyvinylchloride/polyacrylonitrile) polymers. Such membranes are available commercially, for example, in the shape of hollow fibers of various diameters.
Commonly owned U.S. Pat. Nos. 5,101,814 and 5,190,041, and U.S. patent application Ser. No. 08/077,893, the contents of which are incorporated herein by reference, disclose methods by which the electrical activity of living cells encapsulated in a biocompatible semi-permeable membrane of the type discussed above may be measured. This electrical activity may be used to determine the concentration of various constituents in the medium that surrounds the cells or capsule. FIG. 1 shows an example of a recording of the electric potential changes generated by an encapsulated islet of pancreatic beta cells (some alpha and gamma cells may also be incorporated in the islet) responding to a high concentration of glucose in the medium. These electric signals can be measured by electrodes within the membrane capsule, or in its vicinity outside the capsule.
The electric signals generated by the cells are attenuated by the relatively low resistance of the medium as well as the low but significant conductivity of the membrane. The membrane is designed to allow the essential nutrients, gases, excretions etc. to enter or exit the membrane enclosure. Therefore, it is also highly permeable to the ions that make up the electrolytic physiological solution mainly: Na+, K+, Ca++, H+, Mg++, Cl-, OH-, HCOO etc. As these ions carry electric current, the electric resistance of the membrane, which separates the active living cells from the surrounding electrolyte medium, is not high enough to prevent the short-circuiting effect of the medium. For example, a typical hollow fiber membrane made of PVC, 200.mu. in diameter, 50.mu. thick and 1 cm long has an electric resistance (measured from the inside to the outside) of only 2000-5000.OMEGA.. This resistance partially short circuits the electrical signal from the cell mass and makes it difficult to detect the electric signal in the vicinity of the cell mass. Accordingly, a need exists for increasing the electrical resistance of the membrane enclosure to improve the detectability of the signals generated by the cells.
It is an object of the present invention to reduce this short circuiting effect and to thereby increase the measurability of the electrical signals generated by the cell mass.